Valve frame

ABSTRACT

The disclosure relates to support frames for prosthetic implantable valves. The support frames may include a plurality of symmetrically arrayed interconnected U-shaped member structures. Preferred support frames are tubular structures enclosing a longitudinal axis and including a plurality of U-shaped member structures facing a distal or a proximal end of the support frame. Each U-shaped member structure may be connected to a single longitudinally adjacent U-shaped member facing in an opposite longitudinal direction, as well as two laterally adjacent U-shaped members.

PRIORITY CLAIM

This application is a continuation of U.S. patent application Ser. No.12/273,168, which was filed on Nov. 18, 2008 and claims the benefit ofU.S. Provisional Patent Application No. 60/988,987, filed Nov. 19, 2007.The entire contents of each of these related applications are herebyincorporated by reference into this disclosure.

TECHNICAL FIELD

The present disclosure relates to support frames for prostheticimplantable valves adapted for percutaneous implantation within a bodyvessel, as well as methods of treatment pertaining to the implantationof the prosthetic valves and methods of manufacturing prosthetic valves

BACKGROUND OF THE DISCLOSURE

Intraluminally implantable frames may be implanted to treat a variety ofconditions in a variety of fields. Frames implanted in vessels, ducts orchannels of the human body can form part of a valve to regulate fluidflow within a body lumen or as scaffolding to maintain the patency ofthe vessel, duct or channel lumen. Implantable frames can also support avalve or valve leaflets for regulating fluid flow within a body lumen orfor dilating a body lumen. One or more flexible valve leaflets can beattached to an implantable frame to form a medical device useful as anartificial valve. A variety of other implantable prostheses, such asstents, grafts and the like, also comprise an implantable frame placedwithin the body to improve the function of a body lumen.

The venous system includes a series of valves that function to assistthe flow of blood returning to the heart. These natural valves areparticularly important in the lower extremities to prevent blood frompooling in the lower legs and feet during situations, such as standingor sitting, when the weight of the column of blood in the vein can actto prevent positive blood flow toward the heart. This condition,commonly known as chronic venous insufficiency, is primarily found inindividuals in which gradual dilation of the veins, thrombotic events,or other conditions prevent the leaflets of the native valves fromclosing properly. The failure of native valves to properly close canworsen, leading to significant leakage of retrograde flow such that thevalve can become incompetent. Chronic venous insufficiency is acondition in which the symptoms can progress from painful edema to skinulcerations. Elevation of the feet and compression stocking can relievesymptoms, but do not treat the underlying disease. Untreated, thedisease can impact the ability of individuals to perform in theworkplace or maintain their normal lifestyle.

One promising approach to treating venous valve insufficiency includesthe implantation of self-expanding or radially-expandable artificialvalves that can be placed using minimally invasive techniques. Recently,the development of artificial and biological valves has been employed toprovide additional regulation of blood flow within blood vessels, suchas veins. There are a variety of these valves described in the art,which are generally designed to allow normal flow of blood back to theheart, while preventing retrograde flow. However, dynamic fluctuationsin the shape of the vein pose challenges to the design of implantabledevices that conform to the interior shape of the vein. The shape of alumen of a vein can undergo dramatic dynamic change as a result ofvarying blood flow velocities, pressures, and volumes therethrough.Implantable intraluminal prosthetic valves should be compliant enough toconform to the changing shape of the vein lumen and prevent irritationof the wall of the vein contacting the valve, but rigid enough tomaintain vein patency and/or valve function within the vein. Blood flowwithin a vein is intermittent and bidirectional, subject to constantfluctuation in pressure and volume. These conditions may presentchallenges to designing an implantable frame suitable for placementinside the vein. An implantable frame lacking sufficient radial strengthmay collapse and/or fracture under the repeated fluctuations of veindiameter, while an implantable frame with undesirably high levels ofradial strength may lack flexibility and may damage the vein by failingto compress in response to normal fluctuations in the vein diameter.Likewise, an implantable frame with a high surface area contacting theinterior wall of a vein may induce inflammation or trauma in the veinwall, while an implantable frame with an insufficient surface area maylack sufficient durability.

What is needed is an intraluminally-placed medical device, such as asupport frame, that provides structure for an artificial valve and isconfigured to distribute stress and strain forces within the frameduring dynamic movement of a body vessel and intermittent fluid flowwithin the body vessel. In addition, medical devices are needed thatprovide sufficient radial strength to maintain vessel patency whilebeing configured to prevent migration within the body vessel andminimize irritation of the body vessel. There also remains a need for asupport frame configured with a radial strength to maintain patency of abody vessel while supporting a means for regulating fluid within thebody vessel and minimizing irritation to the body vessel afterimplantation and/or extensive wear to the prosthetic valve leafletsduring leaflet motion.

SUMMARY

In a first example, implantable medical devices comprising a supportframe are provided. The support frame may have a proximal annular memberlongitudinally spaced from a distal annular member axially aligned withthe proximal annular member around a longitudinal axis, and plurality oflongitudinal connecting members extending substantially parallel to thelongitudinal axis from the proximal annular member to the distal annularmember. The outer surface of the support frame may define a hypotheticalcircumferential plane and an interior tubular lumen around thelongitudinal axis extending from a proximal end to a distal end of thesupport frame. The support frame may be formed from any biocompatiblematerial, such as a shape memory metal or stainless steel.

The plurality of longitudinal connecting members connecting the proximaland distal annular members is each preferably substantially straight andoriented substantially parallel to each other and the longitudinal axis.The members may have a substantially equal length, and preferably definea portion of the circumferential plane between the distal and proximalannular members. The position of the longitudinal connecting membersaround the circumferential plane of the frame may be selected to providesupport frames with desirable properties, such as improved contactbetween a portion of a valve leaflet and the wall of a body vesseland/or improved symmetrical distribution of stress-strain forces withinthe frame. The support frame may be described with respect to one ormore circumferential distances measured along the circumferential planeperpendicular to the longitudinal axis at a position between theproximal end and the distal end. The support frame may define aplurality of open cells in the hypothetical circumferential planeincluding the abluminal surface of the support frame in communicationwith the lumen defined by the support frame around the longitudinalaxis. For example, the support frame may provide a single open cell inthe circumferential plane extending laterally between two adjacentlongitudinal connecting members opposably positioned across the lumenwith respect to each other.

The support frame may have any suitable number of longitudinalconnecting members. Preferably, the support frame has three or moremembers including at least two members opposably positioned with respectto each other across the lumen. For instance, the plurality oflongitudinal connecting members may consist of three to six straightmembers oriented parallel to the longitudinal axis. Most preferably, thesupport frame includes one or more paired longitudinal connectingmembers extending substantially parallel to the longitudinal axis fromthe proximal annular member to the distal annular member and defining acircumferential plane around the outer surface of the support frame anda tubular lumen around the longitudinal axis and extending from aproximal end to a distal end of the support frame. The plurality ofpaired longitudinal connecting members may consist of (n) pairs ofclosely spaced member pairs including a first member pair opposablypositioned across the lumen from a circumferentially adjacent secondclosely spaced member pair, and (n−2) pairs of closely spaced memberscircumferentially positioned between the first member pair and thesecond member pair, where (n) is an integer of 3 or more.

In a second example, the medical device is a medical device including asupport frame according to the first example, in combination with ameans for regulating fluid flow in a body vessel. The prosthetic valveis preferably an intraluminally-implantable valve prosthesis comprisinga support frame attached to at least one valve leaflet. The prostheticvalve may be a venous valve having a flexible leaflet with avessel-engaging portion. One or more leaflets attached to the supportframe may be formed from an extracellular matrix material or a portionof an explanted tissue valve. The implantable prosthetic valvepreferably includes one or more valve leaflets attached to the supportframe and moveable within the lumen to regulate fluid flow therein. Thevalve leaflet may be attached to the first member and is moveable acrossthe lumen between an open position, permitting fluid flow through thelumen from the proximal end to the distal end, and a closed positionsubstantially preventing fluid flow through the lumen, the valve leafletpreferably contacting the hypothetical circumferential plane oppositethe third member in the closed position.

Delivery systems including a prosthetic valve device and device fordeploying the prosthetic valve, such as a catheter, are also provided.Suitable percutaneous deployment devices may include a balloon catheterhaving adaptations for selectively forcing a portion of the prostheticvalve against the vessel wall, and/or adaptations for radially expandingand compressing the support frame. The prosthetic valve device may bereleasably attached to the deployment device by any suitable meansincluding by the use of adhesives or removable elements such asremovable sutures.

In a third example, methods for treating venous insufficiency areprovided, wherein the method includes deploying a support frame and/or aprosthetic venous valve such as that described above so as to force thevalve body against the vascular wall, and selectively attach edges ofthe valve body against the vascular wall, to seat the valve within thevein. In another aspect of the third example, methods for modifyingblood flow in a vascular vessel are also provided.

Other systems, methods, features and advantages will be, or will become,apparent to one with skill in the art upon examination of the followingfigures and detailed description. It is intended that all suchadditional systems, methods, features and advantages be included withinthis description, be within the scope of the disclosure, and beprotected by the following claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The medical device may be better understood with reference to thefollowing drawings and description. The components in the figures arenot necessarily to scale, emphasis instead being placed uponillustrating the principles of the disclosure. Moreover, in the figures,like referenced numerals designate corresponding parts throughout thedifferent views.

FIG. 1A is a side view of one example of a first support frame.

FIG. 1B is a cross sectional view of a portion of the first supportframe.

FIG. 1C is a flat plan view of the first support frame shown in FIGS. 1Aand 1B.

FIG. 2A is a cross sectional view of a second support frame.

FIG. 2B is a cross sectional view of a third support frame.

FIG. 2C is a cross sectional view of a fourth support frame.

FIG. 3A is a perspective view of a fifth support frame.

FIG. 3B is a cross sectional view of the fifth support frame.

FIG. 3C is a flat plan view of the fifth support frame.

FIG. 4 is a perspective view of a prosthetic valve comprising the fifthsupport frame.

DETAILED DESCRIPTION

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this disclosure pertains. In case of conflict, thepresent document, including definitions, will control. Preferred methodsand materials are described below, although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present disclosure. All publications, patentapplications, patents and other references mentioned herein areincorporated by reference in their entirety. The materials, methods, andexamples disclosed herein are illustrative only and not intended to belimiting.

Definitions

The terms “proximal” and “distal” will be used to describe the opposingaxial ends of the medical device, as well as the axial ends of variouscomponent features. The term “proximal” is used in its conventionalsense to refer to the end of the device (or component thereof) that isclosest to the operator during use of the device. The term “distal” isused in its conventional sense to refer to the end of the device (orcomponent thereof) that is initially inserted into the patient, or thatis closest to the patient.

The term “circumferential” or “circumferentially” refers to a directionor displacement measured along the exterior surface area of an assembledimplantable frame in the expanded configuration that is transverse tothe longitudinal axis of the implantable frame. The recitation of afirst structural feature “circumferentially adjacent” to a secondstructural feature means that the first structural feature is thenearest first structural feature to the second structural feature whenmoving circumferentially along the exterior surface of an implantableframe. The term “circumferential distance” means distance measured alongthe exterior surface of an implantable frame in the expandedconfiguration.

Unless otherwise indicated, the term “longitudinal” or “longitudinally”refers to a direction measured along the longitudinal axis of themedical device, or a portion thereof such as an implantable frame. Theterm “longitudinally opposite” means positioned in a distal or proximaldirection along the exterior surface of a medical device, such as animplantable frame, parallel to the longitudinal axis of the implantableframe. For example, the recitation of a first structural feature“longitudinally adjacent” to a second structural feature of animplantable frame means that the first structural feature is the nearestfirst structural feature to the second structural feature when movinglongitudinally along the exterior surface of the implantable frame.Unless otherwise indicated, the term “longitudinal distance” measuredbetween two structural features of an implantable frame means a distanceor displacement measured parallel to the longitudinal axis of theimplantable frame in the expanded configuration, measured along theexterior surface area of the implantable frame.

Terms such as “preferably,” “desirably,” “commonly,” and “typically” arenot utilized herein to limit the scope of the claimed disclosure or toimply that certain features are critical, essential, or even importantto the structure or function of the claimed disclosure. Rather, theseterms are merely intended to highlight alternative or additionalfeatures that may or may not be utilized in a particular example of thepresent disclosure.

Prosthetic Valves with Preferred Support Frame Configurations

In a first example, implantable medical devices including a supportframe having a preferred geometry are provided. In particular, thesupport frame preferably includes multiple longitudinal connectingmembers circumferentially arranged in particularly preferred positionsrelative to one another. The preferred support frame geometries can beillustrated with respect to the following examples, which serve toillustrate certain preferred aspects of the first example of thedisclosure.

FIG. 1A shows a side view of a first preferred support frame geometry.The support frame 10 may have a proximal annular member 22longitudinally spaced from a distal annular member 20 at the distal end6 of the support frame 10 and axially aligned with the proximal annularmember 22 around a longitudinal axis 2 at the proximal end 4 of thesupport frame 10, as well as a plurality of longitudinal connectingmembers 30 (including 32, 34, 36) extending substantially parallel tothe longitudinal axis 2 from the proximal annular member 22 to thedistal annular member 20. The support frame 10 may define a hypotheticalcircumferential surface plane 12 around the outer surface of the supportframe 10 and a tubular lumen 8 around the longitudinal axis andextending from a proximal end to a distal end of the support frame. Thesupport frame 10 may be formed from any biocompatible material, such asa shape memory metal or stainless steel.

The support frame may have any suitable number of longitudinalconnecting members 30. Preferably, the support frame has three or moremembers including at least two members opposably positioned with respectto each other across the lumen 8. For instance, the plurality oflongitudinal connecting members 30 may consist of three to sixlongitudinal connecting members oriented parallel to the longitudinalaxis 2. The plurality of longitudinal connecting members 30 (“members”)are each preferably substantially straight and oriented substantiallyparallel to each other and the longitudinal axis 2.

In one example, a support frame may have three members orientedsubstantially parallel to one another, with a first circumferentialdistance between the first member and the third member beingsubstantially equal to a second circumferential distance between thethird member and the second member, and the first member and secondmember being opposably positioned and circumferentially adjacent withrespect to each other (e.g., at a radial angle of about 2.pi./2 radianswith respect to one another). FIGS. 1A-1C show a first example of asupport frame 10. The first support frame 10 has three longitudinalconnecting members 30: a first member 32, a second member 34 and a thirdmember 36. The members 30 may have a substantially equal lengths, mayeach be positioned at a substantially equal radial distance from thelongitudinal axis 2 and preferably each define a portion of thehypothetical circumferential surface plane 12 between the distal annularmember 20 and proximal annular member 22. The position of thelongitudinal connecting members 30 around the circumferential plane ofthe frame may be selected to provide support frames 10 with desirableproperties, such as improved contact between a portion of a valveleaflet and the wall of a body vessel and/or improved symmetricaldistribution of stress-strain forces within the frame. The support frame10 may be described with respect to one or more circumferentialdistances measured along the circumferential plane perpendicular to thelongitudinal axis at a position between the proximal end and the distalend.

FIG. 1B is a cross-section of the support frame 10 along line A-A′ shownin FIG. 1A, showing the relative positions of the three members 30. Thefirst member 32 is circumferentially adjacent to the second member 34and the third member 36; the second member 34 is circumferentiallyadjacent to the first member 32 and the third member 36; and the thirdmember 36 is circumferentially adjacent to the first member 32 and thesecond member 34. The first member 32 and the second member 34 areopposably positioned across the lumen 8 defined by the support frame 10.The third member 36 may be positioned at a substantially equalcircumferential distance from the first member 32 and the second member34. A radial angle of about 2.pi./4 is preferably subtended between boththe first member 32 and the third member 36 and between the secondmember 34 and the third member 36. A radial angle of about 2.pi./2 ispreferably subtended between the opposably positioned first member 32and second member 34.

Cylindrical support frames, as shown in FIG. 1A, may be obtained fromthe pattern shown in a flat plan view by cutting the pattern of the flatplan view from a cylindrical tube of the support frame material or froma flat piece of the support frame material, which is then rolled andjoined to form the support frame by any suitable method. Methods ofcutting the flat plan pattern into the support frame material includelaser cutting and chemical etching. Preferably, the support frames arecut from a tube or cannula of shape memory metal to provide a radiallyself-expanding support frame. When forming the support frame from shapememory metal such as nitinol, the support frame can be laser cut from anitinol tube. Thereafter, the support frame can be subjected to ashape-setting process in which the cut tube is expanded on a mandrel andthen heated. Multiple expansion and heating cycles can be used toshape-set the support frame to the final expanded diameter. Preferably,the final expanded diameter is equal to the desired deployed diameter ofthe support frame. During expansion, the support frame is preferablyaxially restrained such that the length of the support frame does notchange during expansion. The finished support frame preferably has anaustenite finish temperature less than body temperature. Thus, at bodytemperature, the support frame will self-expand to the desired deployeddiameter due to the shape memory characteristic of the metal forming thesupport frame.

FIG. 1C shows a flat plan view of the support frame 10 formed byhypothetically “cutting” the support frame 10 along line B-B′ shown inFIG. 1B and “unrolling” the support frame 10 to flatten the hypotheticalcircumferential surface plane 12 described above. The flat plan viewshows the three longitudinal connecting members 30 extending between theproximal annular member 22 and the distal annular member 20, includingthe first member 32 and the third member 36 spaced apart by a firstdistance 42 and the second member 34 and the third member 36 spacedapart by a second distance 44 and the second member 34 spaced from thefirst member 32 by a third distance 48. In the tubular configurationshown in FIG. 1A, the first distance 42, the second distance 44 and thethird distance 46 are circumferential distances measured along thehypothetical circumferential surface plane 12 containing the outer(abluminal) surface of the support frame 10, the circumferentialdistances being measured perpendicular to the longitudinal axis 2 at afixed longitudinal point between the distal end 6 and proximal end 4 ofthe support frame 10.

As shown in FIG. 1A and FIG. 1C, the support frame 10 may define aplurality of open cells in the hypothetical circumferential planeincluding the abluminal surface of the support frame in communicationwith the lumen defined by the support frame around the longitudinalaxis. For example, the support frame may provide a first single opencell in the circumferential plane extending laterally between first (32)and second (34) longitudinal connecting members, which are opposablypositioned across the lumen 8 with respect to each other. Two othersmaller open cells of substantially congruent geometries may be definedby the support frame 10 between the proximal annular member 22 and thedistal annular member 20: a second cell between the first (32) and third(36) members and a third cell between the second (34) and third (36)members (respectively).

In another example, a support frame may have four members orientedsubstantially parallel to one another. For example, FIG. 2A is across-sectional view of a second support frame substantially identicalto the support frame 10 in FIGS. 1A-1C, except as described below. Thesecond support frame includes the first member 32, the second member 34,the third member 36 and a fourth member 38 circumferentially adjacent tothe third member 36 and the second member 34. In this example, thesupport frame may have a first circumferential distance 42′ between thefirst member 32 and the third member 36 substantially equal to a secondcircumferential distance 44 b between the fourth member 38 and thesecond member 34; and a third circumferential distance 44 a between thethird member 36 and the fourth member 38 is less than about 10% of thelongitudinal length of each of the members 30. The support frame in thisexample is also characterized by a fourth circumferential distance 48′between the first member 32 and the second member 34 that issubstantially equal to the sum of the first circumferential distance42′, the second circumferential distance 44 b and the thirdcircumferential distance 44 a. In this example, the third member 36 andthe fourth member 38 are a closely spaced pair of members 30. Supportframes where the plurality of longitudinal connecting members 30includes one or more closely spaced pairs of members are particularlypreferred. It is believed that closely paired support members desirablydistribute stress-strain forces, particularly in radially expandablesupport frames. Additionally, closely paired support members may providefor redundancy in attaching a valve thereto, such as providing a secondsuturing location for securing a valve to the support frame.

Alternatively, the four parallel longitudinal support members in thesecond support frame may be positioned differently, as shown in thecross sectional view of FIG. 2B. The cross section of a third supportframe shown in FIG. 2B is substantially identical to the support frameof FIG. 2A except in the relative circumferential positions of themembers 30. In particular, the third support frame cross section in FIG.2B has a first circumferential distance 42″ between the closely pairedfirst member 32 and the third member 36. A first circumferentialdistance 42″ between the first member 32 and the third member 36 ispreferably less than about 10% of the longitudinal length of the members30. A second circumferential distance 44 b′ is measured between thesecond member 34 and the fourth member 38. A third circumferentialdistance 44 a′ is measured between the third member 36 and the fourthmember 38. A fourth circumferential distance 48″ is measured between thefirst member 32 and the second member 34. The second circumferentialdistance 44 b′ may be substantially equal to the third circumferentialdistance 44 a′ and one-half of the first circumferential distance 42″.The first member 32 is positioned opposite the lumen 8 from the secondmember 34. The radial angle subtended between the fourth member 38 andthe second member 34 is preferably about 2.pi./4. The radial anglesubtended between the fourth member 38 and the third member 36 ispreferably less than 2.pi./4. Preferably, a radial angle of 2.pi./4 issubtended by the sum of (1) the radial angle between the fourth member38 and the third member 36 and (2) one-half of the angle subtendedbetween the first member 32 and the third member 36. The sum of theradial angle between the first member 32 and the second member 34 andone-half of the radial angle subtended between the first member 32 andthe third member 36 is preferably about 2.pi./2.

In another example, the support frame may have five substantiallyparallel members oriented in the manner shown in FIG. 2C. FIG. 2C is across-sectional view of a fourth support frame substantially identicalto the first support frame 10 in FIGS. 1A-1C, except with respect to thenumber and position of the longitudinal connecting members 30 asdescribed below. The plurality of longitudinal connecting members 30 inthe fourth support frame consists of five members oriented substantiallyparallel to one another, including the first member 32, the secondmember 34, the third member 36, a fourth member 38 circumferentiallyadjacent to the third member 36 and a fifth member 39 circumferentiallyadjacent to the second member 34 and the fourth member 38. A firstcircumferential distance 42∝″ extending between the first member 32 andthe third member 36 is preferably less than about 10% of thelongitudinal length of the members. Similarly, a second circumferentialdistance 46 b measured between the second member 34 and the fifth member39 is preferably less than about 10% of the longitudinal length of themembers. A third circumferential distance 44 a″ is measured between thecircumferentially adjacent third member 36 and the fourth member 38. Afourth circumferential distance 48″ is measured between thecircumferentially adjacent fourth member 38 and fifth member 39. Thefirst circumferential distance 42′″ and the second circumferentialdistance 46 b are preferably substantially equal. The thirdcircumferential distance 44 a″ is preferably substantially equal to afourth circumferential distance 46 a between the fourth member 38 andthe fifth member 39. The support frame may also include a fifthcircumferential distance 48′″ between the first member 32 and the secondmember 34 that is substantially equal to the sum of the thirdcircumferential distance 44 a″ and the fourth circumferential distance46 a. A radial angle of about 2.pi./4 radians is subtended by sum of thethird circumferential distance 44 a″ and one half of the firstcircumferential distance 42′″. Similarly, a radial angle of about2.pi./4 radians is subtended by sum of the fourth circumferentialdistance 46 a and one half of the second circumferential distance 46 b.A radial angle of about 2.pi./2 radians is subtended by sum of the fifthcircumferential distance 48″, one half of the first circumferentialdistance 42′″ and one half of the second circumferential distance 46 b.

In another aspect, the support frame has six longitudinal connectingmembers. FIG. 3A shows a perspective view of a fifth support frame 100having a plurality of six longitudinal connecting members 130 extendingbetween a proximal annular member 122 and a distal annular member 120.The fifth support frame 100 differs from the support frames discussedabove in at least two respects: first, the proximal and distal annularmembers (120, 122) are sinusoidal hoop members instead of planar ringmembers and, second, the plurality of longitudinal connecting members130 has six members. In particular, referring to FIG. 3B, the pluralityof longitudinal connecting members may consist of six members 130oriented substantially parallel to one another, including a first member136 b, a second member 134 b, a third member 136 a, a fourth member 132b circumferentially adjacent to the third member 136 a and a fifthmember 132 a, the fifth member 132 a circumferentially adjacent to thefourth member 132 b and a sixth member 134 a, the sixth member 134 acircumferentially adjacent to the fifth member 132 a and the secondmember 134 b. A first circumferential distance 152 c may extend betweenthe first member 136 b and the third member 136 a and be less than about10% of the longitudinal length of the longitudinal connecting members130. A second circumferential distance 152 a may be measured between thesecond member 134 b and the sixth member 134 a and be less than about10% of the longitudinal length of the members 130. A thirdcircumferential distance 152 b may extend between the fourth member 132b and the fifth member 132 a and be less than about 10% of thelongitudinal length of the members 130. A fourth circumferentialdistance 144 may be measured between the third member 136 a and thefourth member 132 b and is preferably substantially equal to a fifthcircumferential distance 142 between the fifth member 132 a and thesixth member 134 a. A sixth circumferential distance 148 is measuredbetween the second member 134 b and the first member 136 b. Preferably,the sixth circumferential distance 148 is substantially equal to the sumof the fourth circumferential distance 144, the third circumferentialdistance 152 b and the fifth circumferential distance 142. The fourthcircumferential distance 144 is preferably substantially equal to thefifth circumferential distance 142.

In one example, the frame may be configured such that when the frame isdeployed within a body vessel, an artificial partial sinus is formedadjacent a valve member such that bodily fluids, for example blood,collecting within the pocket formed around the base of the valve memberare more likely to be flushed out on a continual basis due to theadvantageous geometry created by the valve member and artificial partialsinus.

For example, an artificial partial sinus may be formed by at least oneof the longitudinal connecting members. Referring again to FIG. 3A, thefifth member 132 a and the fourth member 132 b may create an artificialpartial sinus. The artificial partial sinus is preferably characterizedby a greater lateral distance between a portion of the longitudinalconnecting members (132 a, 132 b) and the longitudinal axis 102 thanbetween proximal and distal annular members (120, 122) and thelongitudinal axis 102. The partial sinus is preferably formed by thelongitudinal connecting members (132 a, 132 b) curving or arching awayfrom the lumen 108.

The configuration of the partial sinus may depend on several factors,including body vessel diameter, valve member geometry such as length,slack, and orientation, fluid column pressures at the site ofdeployment, and other factors. For example, the partial sinus may have alongitudinal length at least as great as the longitudinal length of thevalve member, permitting the valve member to fully retract within thepartial sinus, thereby substantially uninterrupting antegrade flow.

The support frames preferably include one or more paired longitudinalconnecting members extending substantially parallel to the longitudinalaxis from the proximal annular member to the distal annular member anddefining a circumferential plane around the outer surface of the supportframe and a tubular lumen around the longitudinal axis and extendingfrom a proximal end to a distal end of the support frame. The pluralityof paired longitudinal connecting members may consist of (n) pairs ofclosely spaced member pairs including a first closely-spaced member pairopposably positioned across the lumen from a circumferentially adjacentsecond closely spaced member pair, and (n−2) pairs of closely spacedmembers circumferentially positioned between the first closely-spacedmember pair and the second member pair, where (n) is an integer of 3 ormore. Preferably, (n) is an integer of 3 or more, including integers of3, 4, 5, 6, 7, 8, 9, 10 or more.

As used herein, “closely-spaced pairs” of longitudinal connectingmembers are circumferentially adjacent longitudinal connecting membersthat are circumferentially separated by a distance that is less thanabout 15% of their length, and preferably less than 10%. Pairs ofclosely-spaced longitudinal connecting members are preferably positionedat substantially equal circumferential distances from circumferentiallyadjacent pairs of longitudinal connecting members. The circumferentialdistance between each pair of closely spaced members is preferably lessthan about 10% of the longitudinal length of the members. For examplewhen (n) is 3, the support frame may include a third closely spacedmember pair positioned symmetrically between the first member pair andthe second member pair, the support frame having a first circumferentialdistance between the first member pair and the third member pair that issubstantially equal to a second circumferential distance between thethird member pair and the second member pair.

FIG. 3B is a cross sectional view of the fifth support frame 100 betweenthe proximal annular member 122 and the distal annular member 120. Thesixth support frame 100 includes three closely spaced pairs oflongitudinal connecting members. The plurality of paired longitudinalconnecting members 130 extend substantially parallel to the longitudinalaxis from the proximal annular member 122 to the distal annular member120 and define a hypothetical circumferential plane around the outersurface of the support frame 100 and a tubular lumen 108 around thelongitudinal axis 102 and extending from a proximal end 104 to a distalend 106 of the support frame 100. The first circumferential distance 152c, the second circumferential distance 152 a and the thirdcircumferential distance 152 b are all preferably substantially equal,and are each preferably less than about 10% of the longitudinal lengthof any of the members 130. The close spacing of the first and thirdmembers (136 a, 136 b), the fourth and fifth members (132 a, 132 b)and/or the second and sixth members (134 a, 134 b) desirably distributesstress and strain sustained at the connections between the longitudinalconnecting members 130 to the proximal annular member 122 and the distalannular member 120, particular during radial compression of the supportframe 100. Additionally, close spacing of the members, for example thefirst and third members (136 a, 136 b), the fourth and fifth members(132 a, 132 b) and/or the second and sixth members (134 a, 134 b), mayprovide for redundancy in attaching a valve thereto, such as providing asecond suturing location for securing a valve to the support frame.

Alternative examples provide support frames with two, three, four, five,six or more pairs of longitudinal connecting members. Preferably, atleast two pairs of circumferentially adjacent longitudinal connectingmembers are positioned across the lumen 108 from each other.

FIG. 3C is a flat plan view of the fifth support frame 100, formed bytheoretically “cutting” the cross section of FIG. 3B along line B-B′ and“unrolling” the support frame 100 into a flat plane corresponding to thehypothetical circumferential plane forming the outer surface of thesupport frame 100 in the tubular configuration shown in FIG. 3A.Alternatively, the tubular support frame 100 may be formed by lasercutting a cylindrical cannula of biocompatible metal according to thepattern shown in FIG. 3C. The support frame 100 has a total longitudinallength 160. The proximal annular member 122 and distal annular member120 are spaced apart by a first longitudinal distance 164. The pluralityof six longitudinal connecting members 130 each has a substantiallyequal length 162. The support frame 100 also includes three reinforcingmembers 124. The reinforcing members 124 are joined at both ends to asingle annular member, such as the distal annular member 120 or theproximal annular member 122, and can have the same or different shapes.

Implantable Support Frame Compositions

The support frame may be formed from any suitable material. Preferredmaterials for frames include those materials that can provide thedesired functional characteristics with respect to mechanical loadbearing, biological compatibility, modulus of elasticity, radio-opacity,or other desired properties. For some examples, the materials used toform the implantable frames can comprise a material that exhibitsexcellent corrosion resistance. For some examples, the material can beselected to be sufficiently radiopaque and create minimal artifactsduring magnetic resonance imaging techniques (MRI). In some examples,the implantable frame can comprise a metal, a metal alloy, a polymer, orany suitable combination thereof, for example as frame with multiplelayers.

Preferably, the support frames are self-expanding comprising a materialcapable of significant recoverable strain to assume a low profile fordelivery to a desired location within a body lumen. After release of thecompressed self-expanding stent, it is preferred that the frame becapable of radially expanding back to its original diameter or close toits original diameter. Accordingly, some examples provide frames madefrom material with a low yield stress (to make the frame deformable atmanageable balloon pressures), high elastic modulus (for minimalrecoil), and is work hardened through expansion for high strength.Particularly preferred materials for self-expanding implantable framesare shape memory alloys that exhibit superelastic behavior, i.e., arecapable of significant distortion without plastic deformation. Framesmanufactured of such materials may be significantly compressed withoutpermanent plastic deformation, i.e., they are compressed such that themaximum strain level in the stent is below the recoverable strain limitof the material. Discussions relating to nickel titanium alloys andother alloys that exhibit behaviors suitable for frames can be found in,e.g., U.S. Pat. No. 5,597,378 (Jervis) and WO 95/31945 (Burmeister etal.). A preferred shape memory alloy is Ni—Ti, although any of the otherknown shape memory alloys may be used as well. Such other alloysinclude: Au—Cd, Cu—Zn, In—Ti, Cu—Zn—Al, Ti—Nb, Au—Cu—Zn, Cu—Zn—Sn,CuZn—Si, Cu—Al—Ni, Ag—Cd, Cu—Sn, Cu—Zn—Ga, Ni—Al, Fe—Pt, U—Nb, Ti—Pd—Ni,Fe—Mn—Si, and the like. These alloys may also be doped with smallamounts of other elements for various property modifications as may bedesired and as is known in the art. Nickel titanium alloys suitable foruse in manufacturing implantable frames can be obtained from, e.g.,Memry Corp., Bethel, Conn. One suitable material possessing desirablecharacteristics for self-expansion is Nitinol, a Nickel-Titanium alloythat can recover elastic deformations of up to 10 percent. Thisunusually large elastic range is commonly known as superelasticity.

Alternatively, the implantable frames are designed to be expanded by aballoon or some other device (i.e., the frames are not self-expanding),and may be manufactured from an inert, biocompatible material with highcorrosion resistance that can be plastically deformed at low-moderatestress levels, such as tantalum. The implantable frames can be deployedby both assisted (mechanical) expansion, e.g. balloon expansion, andself-expansion means. In examples where the implantable frame isdeployed by mechanical (balloon) expansion, the implantable frame ismade from materials that can be plastically deformed through theexpansion of a mechanical assist device, such as by the inflation of acatheter based balloon. When the balloon is deflated, the frame canremain substantially in the expanded shape. Other acceptable materialsinclude stainless steel, titanium ASTM F63-83 Grade 1, niobium or highcarat gold K 19-22. One widely used material for balloon expandablestructures is stainless steel, particularly 304 and 316L stainlesssteel. This material is particularly corrosion resistant with a lowcarbon content and additions of molybdenum and niobium. Fully annealed,stainless steel is easily deformable. Alternative materials formechanically expandable structural frames that maintain similarcharacteristics to stainless steel include tantalum, platinum alloys,niobium alloys, and cobalt alloys.

Optionally, the support frame may be formed from or coated with othermaterials, such as polymers and bioabsorbable polymers may be includedin or on the implantable support frames. The support frames or portionsthereof can optionally comprise material that permits identification ofthe position or orientation of the frame within a body passage.Radiopaque markers are advantageously positioned at one or more ends ofthe implantable frame to aid the physician in positioning the frame at asite inside a body vessel. For example, portions of the implantableframe can include a radiopaque material that can be identified byX-rays. For example, U.S. Pat. No. 6,409,752, issued Jun. 25, 2002 toBoatman et al., incorporated herein by reference, discloses variousradiopaque materials that can be used in or on the implantable frames.

The implantable frames may be fabricated using any suitable method knownin the art. Preferably, the complete frame structure is cut from a solidtube or sheet of material, and thus the frame would be considered amonolithic unit. Laser cutting, water-jet cutting and photochemicaletching are all methods that can be employed to form the structuralframe from sheet and tube stock. Still other methods for fabricating thecomplete frame structure as previously disclosed would be understood byone of skill in the art.

Alternatively, the frame can also be formed from wire using wire formingtechniques, such as coiling, braiding, or knitting. By welding the wireat specific locations a closed-cell structure may be created. Thisallows for continuous production, i.e. the components of the implantableframe may be cut to length from a long wire mesh tube. In addition, animplantable frame is constructed from sheet, wire (round or flat) ortubing. The method of fabrication can be selected by one skilled in theart depending on the raw material used. Techniques for formingimplantable frames are discussed, for example, in Dougal et al., “StentDesign: Implications for Restenosis,” Rev. Cardiovasc Med. 3 (suppl. 5),S16-S22 (2002), which is incorporated herein by reference in itsentirety.

In some examples, connections between the U-shaped member of eachportion to the U-shaped member of an adjacent portion in mirror symmetryat the first and second connections, as well as the connection betweenthe supporting arms and the U-shaped member and the struts 32 and bendsof the supporting arms, may be by welding or other suitable connectingmeans. Other connection means include the use of a binder, heat, orchemical bond, and/or attachment by mechanical means, such as pressing,welding or suturing. In addition, portions of the frame may be attachedby applying a bonding coating.

A support frame can optionally be sterilized using any suitabletechnique known in the art, or equivalents thereto. For example, animplantable frame can be sterilized using ethylene oxide sterilization,as described in AAM/ISO 11135:1994 “Medical Devices—Validation andRoutine Control of Ethylene Oxide Sterilization,” incorporated herein byreference in its entirety. In some examples, a sterilized implantableframe satisfies a minimum Sterility Assurance Level (SAL) of about10.sup.−6.

Prosthetic Valve Devices

In a second example, prosthetic valve devices are provided. Theprosthetic valve preferably includes a support frame described withrespect to the first example and a means for regulating fluid through abody vessel. Preferably the prosthetic valve prosthesis devices areconfigured to treat incompetent or damaged cardiac or venous valves inmammals or to otherwise beneficially modify fluid flow in a bodilypassage. For example, a prosthetic valve may be configured to replace oraugment the function of natural venous valves operative in veins. Theprosthetic venous valve preferably includes a support frame of the firstexample designed to resist collapsing under the contraction of themuscle present around veins by symmetrically distributing stress andstrain within the frame.

A second non-limiting example of a suitable prosthetic valve device 300is shown in FIG. 4, which includes a flexible valve member attached to afirst tubular support frame described above with respect to FIGS. 3A-3C.Other prosthetic valves can be formed by attaching a means forregulating fluid flow, such as a valve leaflet or monocuspid valvemember, to any support frame described according to the first example.One or more prosthetic valves can be implanted within a tubular bodypassage of a patient, especially a human, including for example in veinsor arteries, to regulate fluid flow therein.

With reference to FIG. 4, a prosthetic valve 300 includes a supportframe 310, which may be similar to the frame 100 described above, withsix longitudinal connecting members 330 extending between a proximalannular member 322 and a distal annular member 320. Support frame 310includes a proximal annular member 322 that differs from the proximalannular member 122 in that the member 124 forms part of the annularmember 322. A valve member, such as monocuspid valve member 350 isattached to the support frame 310. The monocuspid valve member 350 isconfigured and attached in a manner to allow a portion of the monocuspidvalve member 350 to extend across the lumen 308 of the support frame310. Preferably, the support frame 310 is radially self-expanding with amaximum diameter that is slightly greater than the body vessel where theprosthetic valve 300 is implanted, such that the support frame 310exerts sufficient outward radial force against the inner wall of thebody vessel to retain the prosthetic valve 300 therein. Alternatively,the support frame 310 may include one or more means to anchor thesupport frame 310 within a body vessel, such as barbs or adhesivesdisposed on the outer, vessel-contacting portion of the support frame320 (not shown).

Support frames where the plurality of longitudinal connecting membersincludes one or more circumferentially adjacent pairs of membersseparated by a circumferential distance that is less than the length ofthe members are particularly preferred. Preferably, two or morecircumferentially adjacent longitudinal connecting members are closelyspaced member pairs. It is believed that closely paired support membersdesirably distribute stress-strain forces, particularly in radiallyexpandable support frames.

In a vein, blood flow occurs in an intermittent nature, with surges inantegrade fluid flow occurring between intermittent retrograde fluidflow. A prosthetic venous valve 300 preferably provides a one-way valvethat permits intermittent blood flow in an antegrade direction 309 whileminimizing the retrograde fluid flow in the opposite direction 307. Themonocuspid valve member 350 is a flexible structure configured tomoveably traverse the lumen 308 of the support frame 310, and configuredto sealably engage the opposite wall of the vein through a portion ofthe opposite side of the support frame 310. In this example, wear on thevalve member may be decreased and may provide for improved sealingagainst the wall of the vein. The monocuspid valve member 350 may beconfigured as a single leaflet attached to a first closely-spaced pairof longitudinal connecting members 332 a and 332 b and a secondclosely-spaced pair of longitudinal connecting member 334 a and 334 b,which may be positioned opposite one another across the lumen 308. Themonocuspid valve member 350 can be formed from a suitably flexiblematerial that is responsive to fluid flow contacting the surface, andcan be sized to extend transversely across the lumen 308 of the supportframe 310, in a path substantially perpendicular to the longitudinalaxis 302.

The monocuspid valve member 350 can be oriented with the retrogradesurface of the leaflet facing the direction of longitudinal retrogradefluid flow through lumen 308. For example, in a vein, the direction ofretrograde fluid flow 307 is away from the heart, while antegrade fluidflow direction 309 proceeds along the longitudinal axis 302 in thedirection toward the heart. During retrograde fluid flow 307, bloodpasses the free edge 351 (unattached to the support frame 310) of themonocuspid valve member 350, urging the leading edge to transverselycross the lumen 308 and sealably engage the vein wall as blood fills themonocuspid valve member 350. The monocuspid valve member 350 may have aclosed or substantially closed end and an open end (e.g., free edge351). The monocuspid valve member 350 quickly fills with the retrogradeflowing blood, decreasing blood flow through the prosthetic valve 300 inthe retrograde direction 307 to assume the closed configuration shown inFIG. 4. In the closed configuration, blood fills the “pocket” 354 of themonocuspid valve member 350, which completely fills the lumen 308 andminimizes fluid flow through the prosthetic valve 300 in the retrogradedirection 307.

When blood flow in the antegrade direction 309 occurs, blood exertspressure on the antegrade surface of the monocuspid valve member 350,urging the free edge 351 back across the lumen 308 and forcing out fluidcollected in the pocket 354 portion of the monocuspid valve member 350.As the monocuspid valve member 350 opens, the free edge 351 is forcedtoward vessel wall, opening the prosthetic valve 300 and allowing bloodto flow in an antegrade direction 309.

Alternatively, a multicusp leaflet configuration may be utilized in theprosthetic valve 300, with the prosthetic valve having multiple leafletsconfigured in such a manner to allow the leaflets to co-apt within thelumen 308 of the support frame 310. The valve leaflets can have anysuitable shape. Preferably, the valve leaflet includes one or more edgesattached to a valve support frame 310 and extend within the lumen 308.The valve leaflets preferably have (n) edges and (n−1) edges of eachvalve leaflet preferably contact the support frame 310, where (n) is aninteger equal to 2 or greater. Valve leaflets with (n) of 2, 3, or 4 arepreferred, although leaflets with other shapes can also be used.Preferably, at least 2 edges of a valve leaflet are attached to a valvesupport frame 310, and at least one edge of a valve leaflet is a leafletfree edge that is not attached to any support frame.

A wide variety of materials acceptable for use as a valve member orvalve leaflet are known in the art, and any suitable material can beutilized. The material chosen need only be able to perform as describedherein, and be biocompatible, or able to be made biocompatible. Examplesof suitable materials include natural materials, and syntheticmaterials.

In certain examples of the disclosure, the leaflet is formed from aflexible material comprising a naturally derived or syntheticcollagenous material, and especially an extracellular collagen matrixmaterial. Examples of suitable natural materials include collagen andextracellular matrix (ECM) material, such as submucosa. The“extracellular matrix” is typically a collagen-rich substance that isfound in between cells in animal tissue and serves as a structuralelement in tissues. Such an extracellular matrix is preferably a complexmixture of polysaccharides and proteins secreted by cells. Theextracellular matrix can be isolated and treated in a variety of ways.Following isolation and treatment, it is referred to as an ECM. ECM maybe isolated from submucosa (including small intestine submucosa),stomach submucosa, urinary bladder submucosa, tissue mucosa, renalcapsule, dura mater, liver basement membrane, pericardium or othertissues. One specific example of ECM is small intestine submucose (SIS).When implanted, SIS can undergo remodeling and can induce the growth ofendogenous tissues upon implantation into a host. SIS has been usedsuccessfully in vascular grafts, urinary bladder and hernia repair,replacement and repair of tendons and ligaments, and dermal grafts. SISis particularly well-suited for use as valve members, such as leaflets.Suitable extracellular matrix materials (“ECM material”) include, forinstance, submucosa (including, for example, small intestinal submucosa(“SIS”), stomach submucosa, urinary bladder submucosa, or uterinesubmucosa), renal capsule membrane, dura mater, pericardium, serosa, andperitoneum or basement membrane materials, including liver basementmembrane. These layers may be isolated and used as intact natural sheetforms, or reconstituted collagen layers including collagen derived fromthese materials or other collagenous materials may be used. Foradditional information as to submucosa materials useful in the presentdisclosure, and their isolation and treatment, reference can be made toU.S. Pat. Nos. 4,902,508, 5,554,389, 5,993,844, 6,206,931, and6,099,567, the contents of which are incorporated herein by reference.Renal capsule tissue can also be obtained from warm blooded vertebrates,as described more particularly in copending U.S. patent application Ser.No. 10/186,150, filed Jun. 28, 2002, and International PatentApplication Serial Number PCT/US02/20499, filed Jun. 28, 2002, andpublished Jan. 9, 2003 as International Publication Number WO/03002165,the contents of which are incorporated herein by reference. In oneexample of the disclosure, the ECM material is porcine SIS. SIS can beprepared according to the method disclosed in U.S. 2004/0180042A1,published Sep. 16, 2004, the contents of which are incorporated hereinby reference. In addition to xenogenic biomaterials, such as SIS,autologous tissue can be harvested as well. Additionally Elastin orElastin Like Polypeptides (ELPs) and the like offer potential as amaterial to fabricate the flexible covering or discrete shaping membersto form a device with exceptional biocompatibility. Another alternativeis use of allographs such as harvested native valve tissue. Such tissueis commercially available in a cryopreserved state.

In one aspect, the valve member, and preferably a valve leaflet, isformed from explanted biological tissue, such as aortic tissue, that istreated in a manner that improves the biocompatibility of the tissue foran intended use. For example, the tissue may be treated to improveresistance to post-implantation mineralization. One preferred method isdescribed in U.S. Pat. No. 5,595,571 (Filed Apr. 18, 1994), incorporatedby reference herein in its entirety, which involves exposing biologicalmaterial including cellular and non-cellular structural components to abuffered solution having a pH in the range from about 5.0 to about 8.0and a temperature in the range from about 12.degree. C. to about30.degree. C. for a sufficient amount of time to facilitate thedegradation of cells by autolytic enzymes within the cells, whereby atleast one region of the biological material is rendered substantiallyacellular while preserving the overall structural integrity andnon-cellular structural components of the biological material Theexposure occurs prior to any fixation of the biological material. Othersuitable tissue treatments are described in the following references,all of which are incorporated herein by reference in their entirety:U.S. Pat. Nos. 5,720,777, 5,843,180 and 5,843,181 (Biological MaterialPre-fixation Treatment); 4,798,611 (Enhancement of Xenogenic Tissue bytreatment with glutaraldehyde and then irradiation); 4,813,958(Crosslinked anisotropic mammalian diaphragm in surgicalreconstruction); 3,966,401 (Tissue for Implantation so as to ProvideImproved Flexibility by Tissue subjecting tissue to tanning fluid whenunder pressure until the tissue assumes a natural configuration duringtanning in Tanning fluids including 4% formaldehyde and 2%glutaraldehyde); 4,800,603 (Tissue Fixation with Vapor by subjectingtissue to a vapor of a fixative while the tissue is unstressed); and4,813,964 and 4,813,958 (Crosslinked anisotropic xenogenic diaphragmtissue in flexor tendon pulley reconstruction, such as a method oftissue replacement for nonfunctional flexor tendon pulleys includingreplacing the flexor tendon pulleys with anisotropic, crosslinkedmammalian, bovine or porcine diaphragm which is characterized in thatthe diaphragm has one smooth side and one fibrous side, the smooth sidebeing placed against the flexor tendon). Preferably, the explantedtissue explanted tissue is pre-treated by performing at least one of thefollowing steps: maintaining the explanted tissue at a pH in the rangefrom about 5.0 to about 8.0 and a temperature in the range from about12.degree. C. to about 30.degree. C. for a sufficient amount of timesufficient to effect the degradation of at least a portion of the cellsby autolytic enzymes within the cells; contacting the explanted tissuewith a chemical cross-linking agent and then irradiating with X-ray orgamma radiation; contacting the explanted tissue with a tanning fluidincluding formaldehyde or glutaraldehyde; or placing tissue explantedtissue within an atmosphere of substantially unpressurized vapor ofcontaining glutaraldehyde, and maintaining the tissue within theatmosphere of substantially unpressurized vapor in a manner sufficientto provide substantially uniform application of the fixative solutionfor a period of time to cause the desired fixation of said tissue.

The valve leaflet may be formed from a synthetic polymeric material.Examples of suitable polymeric materials include polyesters, such aspoly(ethylene terephthalate), polylactide, polyglycolide and copolymersthereof; fluorinated polymers, such as polytetrafluoroethylene (PTFE),expanded PTFE and poly(vinylidene fluoride); polysiloxanes, includingpolydimethyl siloxane; and polyurethanes, including polyetherurethanes,polyurethane ureas, polyetherurethane ureas, polyurethanes containingcarbonate linkages and polyurethanes containing siloxane segments. Inaddition, materials that are not inherently biocompatible may besubjected to surface modifications in order to render the materialsbiocompatible. Examples of surface modifications include graftpolymerization of biocompatible polymers from the material surface,coating of the surface with a crosslinked biocompatible polymer,chemical modification with biocompatible functional groups, andimmobilization of a compatibilizing agent such as heparin or othersubstances.

In addition, the valve leaflet material may be a biocompatiblepolyurethane or derivative thereof. One example of a biocompatiblepolyurethane is THORALON (THORATEC, Pleasanton, Calif.), as described inU.S. Pat. Application Publication No. 2002/0065552 A1 and U.S. Pat. No.4,675,361, both of which are incorporated herein by reference. Accordingto these patents, THORALON is a polyurethane base polymer (referred toas BPS-215) blended with a siloxane containing surface modifyingadditive (referred to as SMA-300). Base polymers containing urealinkages can also be used. The concentration of the surface modifyingadditive may be in the range of 0.5% to 5% by weight of the basepolymer. The SMA-300 component (THORATEC) is a polyurethane comprisingpolydimethylsiloxane as a soft segment and the reaction product ofdiphenylmethane diisocyanate (MDI) and 1,4-butanediol as a hard segment.A process for synthesizing SMA-300 is described, for example, in U.S.Pat. Nos. 4,861,830 and 4,675,361, which are incorporated herein byreference. The BPS-215 component (THORATEC) is a segmentedpolyetherurethane urea containing a soft segment and a hard segment. Thesoft segment is made of polytetramethylene oxide (PTMO), and the hardsegment is made from the reaction of 4,4′-diphenylmethane diisocyanate(MDI) and ethylene diamine (ED). THORALON can be manipulated to provideeither porous or non-porous THORALON. Porous THORALON can be formed bymixing the polyetherurethane urea (BPS-215), the surface modifyingadditive (SMA-300) and a particulate substance in a solvent. Theparticulate may be any of a variety of different particulates or poreforming agents, including inorganic salts, which may be removed bycontacting the material with a suitable solvent to dissolve and removethe inorganic salt after pore formation. Formation of porous THORALON isdescribed, for example, in U.S. Pat. Nos. 6,752,826 and 2003/0149471 A1,both of which are incorporated herein by reference. Non-porous THORALONcan be formed by mixing the polyetherurethane urea (BPS-215) and thesurface modifying additive (SMA-300) in a suitable solvent, such asdimethyacetamide (DMAC). The composition can contain from about 5 wt %to about 40 wt % polymer, and different levels of polymer within therange can be used to fine tune the viscosity needed for a given process.The composition can contain less than 5 wt % polymer for some sprayapplication examples. The entire composition can be cast as a sheet, orcoated onto an article such as a mandrel or a mold to form a valveleaflet, which can be dried to remove the solvent.

Returning to the prosthetic valve 300 example described with respect toFIG. 4, the monocuspid valve member 350 or two or more valve leafletsmay be securably mounted to the support frame 310 by any suitable means.The valve leaflet material can be attached to the support structure byany appropriate attachment means, including but not limited to,adhesive, fasteners, suturing, and tissue welding using heat and/orpressure. In one example, the valve member 350 or two or more valveleaflets is sutured to the longitudinal connecting members.Additionally, where the longitudinal connecting members are closelypaired support members, the valve member or two or more valve leafletsmay be sutured to both closely paired support members, thereby providingfor redundancy in attaching the valve to the support frame 310.

Alternatively, the valve leaflet may be formed on the support structureby an appropriate means, including but not limited to vapor deposition,spraying, electrostatic deposition, ultrasonic deposition, or dipping.One or more valve leaflets can be attached to the support frame by othermethods. In one example, a sheet of material is cut to form a valveleaflet and the edges of the leaflet are wrapped around portions of asupport frame and portions of the valve leaflet sealably connectedtogether to fasten the valve leaflet around the support frame. Forexample, one edge of a sheet of valve leaflet material can be wrappedaround a portion of the support frame and held against the body of thevalve leaflet, so that the valve leaflet material forms a lumenenclosing a portion of the support frame. A small amount of a suitablesolvent is then applied to the edge of the valve leaflet material todissolve the edge into an adjacent portion of the valve leaflet materialand thereby seal the material around the support frame.

In another example, the sheet of valve leaflet material is shaped toform the valve leaflet that is attached to a portion of a support frameusing stitching through the valve leaflet material and around a portionof the support structure, adhesives, tissue welding or cross linking todirectly join the valve leaflet material to the support frame. A valveleaflet attached to a support frame can be permitted to move relative tothe support frame, or the valve leaflet can be substantially fixed inits position or orientation with respect to the support frame by usingattachment configurations that resist relative movement of the valveleaflet and the support frame.

Other prosthetic valves can be formed by attaching a means forregulating fluid flow, such as a valve leaflet or monocuspid valvemember, to any support frame described according to the first example.One or more prosthetic valves can be implanted within a tubular bodypassage of a patient, especially a human, including for example in veinsor arteries, to regulate fluid flow therein.

Methods of Delivery and Treatment

Artificial valve prostheses can be deployed at various locations andlumens in the body, such as, for example, coronary, vascular,nonvascular and peripheral vessels, ducts, and the like. In one example,a valve leaflet is attached to the support frame to provide animplantable valve prosthesis that can be implanted within a vein, forinstance, near an incompetent venous valve to treat venous valveinsufficiency. Prosthetic valve devices of the present disclosure aredesirably adapted for deployment within the vascular system, and incertain preferred examples, are adapted for deployment within the venoussystem. Accordingly, a prosthetic valve can be adapted as a venousvalve, for example, for attachment within veins of the legs or feet, totreat venous insufficiency.

The prosthetic valves described herein can be configured for delivery toa body vessel in a radially compressed configuration, and radiallyexpanded at a point of treatment within the body vessel. The overallconfiguration, cross-sectional area, and length of a medical deviceframe having a tubular configuration (compressed or expanded) may dependon several factors, including the size and configuration of device, thesize and configuration of the vessel in which the device will beimplanted, the extent of contact between the device and the walls of thevessel, and the amount of retrograde flow through the vessel that isdesired.

Preferably, the support frames and/or prosthetic valves described abovecan be radially intraluminally delivered inside the body by a catheterthat supports the implantable frame in a compressed form as it istransported to the desired site, for example within a body vessel. Uponreaching the site, the implantable support frame can be expanded andsecurably placed within the body vessel, for example by securablyengaging the walls of the body vessel lumen. The expansion mechanism mayinvolve permitting the support frame to expand radially outward, forexample, by inflation of a balloon formed in the distal portion of thecatheter, to inelastically deform the frame and fix it at apredetermined expanded position in contact with the lumen wall. Theexpansion balloon can then be deflated and the catheter removed. Inanother technique, the implantable support frame is formed of a materialthat will self-expand after being compressed. During introduction intothe body, the implantable support frame is restrained in the compressedcondition. When the stent has been delivered to the desired site forimplantation, the restraint is removed, allowing the implantable frameto self-expand by its own internal elastic restoring force. Once theimplantable frame is located at the constricted portion of the lumen,the sheath is removed to expose the frame, which is expanded so itcontacts the lumen wall. The catheter is subsequently removed from thebody by pulling it in the proximal direction, through the larger lumendiameter created by the expanded prosthesis, which is left in the body.

Implantable frames or prostheses comprising the implantable frame can bedelivered into a body lumen using a system which includes a catheter. Anappropriately sized delivery catheter can be selected by one skilled inthe art for a given application. For example, some examples can bedelivered using a delivery catheter selected from one or more deliverycatheter sizes from the group consisting of: 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 French (F)delivery catheters, or increments of 0.1 F therebetween. In someexamples, a delivery catheter sized between 3 and 24 F, or preferablybetween about 6 F and 16 F can be used.

The implantable support frames and/or prosthetic valves can be placed inany medically appropriate location for a given application. For example,in some examples, the implantable frame can serve as part of a venousvalve prosthetic and be implanted in the femoral vein, including at theproximal (groin), mid (mid section) or distal (adjacent to the knee)portions of the vein. Preferably, prosthetic valves are placed in thesuperficial venous system, such as the saphenous veins in the leg, or inthe deep venous system, such as the femoral and popliteal veinsextending along the back of the knee to the groin.

Methods of treatment preferably include the steps of loading aprosthetic valve in a radially compressed configuration into a deliverycatheter, inserting the delivery catheter into a body vessel,translating the delivery catheter to a treatment site, deploying theartificial valve prosthesis by placing the artificial valve prosthesisin an expanded configuration at the treatment site to treat the subject,and withdrawing the delivery catheter from the body vessel.

Having described the disclosure in detail and by reference to specificexamples thereof, it will be apparent that modifications and variationsare possible without departing from the scope of the disclosure definedin the appended claims. More specifically, although some aspects of thepresent disclosure are identified herein as preferred or particularlyadvantageous, it is contemplated that the present disclosure is notnecessarily limited to these preferred aspects of the disclosure. It istherefore intended that the foregoing detailed description be regardedas illustrative rather than limiting, and that it be understood that itis the following claims, including all equivalents, that are intended todefine the spirit and scope of this disclosure.

We claim:
 1. A support frame suitable for prosthetic implantable valvescomprising: a proximal annular member longitudinally spaced from adistal annular member axially aligned with the proximal annular memberaround a longitudinal axis; a plurality of longitudinal connectingmembers extending substantially parallel to the longitudinal axis fromthe proximal annular member to the distal annular member and defining ahypothetical circumferential plane around an outer surface of thesupport frame and defining a lumen extending from a proximal end to adistal end of the support frame around the longitudinal axis; theplurality of longitudinal connecting members including a first memberopposably positioned across the lumen from a directly circumferentiallyadjacent second member without an intervening member disposedtherebetween, a third member circumferentially adjacent to the firstmember, and a fourth member circumferentially adjacent to the thirdmember; wherein a first circumferential distance is disposed between thefirst member and the second member, a second circumferential distance isdisposed between the third member and the first member, and a thirdcircumferential distance is disposed between the third member and thefourth member; wherein the first circumferential distance is greaterthan each of the second circumferential distance and the thirdcircumferential distance; and wherein the circumferential distances aremeasured along the circumferential plane perpendicular to thelongitudinal axis at a position between the proximal end and the distalend.
 2. The frame of claim 1, wherein the fourth member iscircumferentially adjacent to the second member; wherein a fourthcircumferential distance is disposed between the fourth member and thesecond member; wherein the first circumferential distance is greaterthan the fourth circumferential distance; wherein the secondcircumferential distance between the first member and the third memberis substantially equal to the fourth circumferential distance betweenthe fourth member and the second member; and wherein the firstcircumferential distance between the first member and the second memberis substantially equal to the sum of the second circumferentialdistance, the third circumferential distance, and the fourthcircumferential distance.
 3. The frame of claim 1, wherein the fourthmember is circumferentially adjacent to the second member; wherein afourth circumferential distance is disposed between the fourth memberand the second member; wherein the first circumferential distance isgreater than the fourth circumferential distance; and wherein the fourthcircumferential distance between the fourth member and the second memberis substantially equal to the third circumferential distance andone-half of the second circumferential distance.
 4. The frame of claim1, further comprising a fifth member circumferentially adjacent to thefourth member and the second member; wherein a fourth circumferentialdistance is disposed between the fourth member and the fifth member;wherein a fifth circumferential distance is disposed between the fifthmember and the second member; wherein the first circumferential distanceis greater than the fourth circumferential distance; and wherein thefirst circumferential distance is greater than the fifth circumferentialdistance.
 5. The frame of claim 4, wherein the second circumferentialdistance is substantially equal to the fifth circumferential distance;and wherein the third circumferential distance is substantially equal tothe fourth circumferential distance.
 6. The frame of claim 5, whereinthe first circumferential distance between the first member and thesecond member is substantially equal to the sum of the thirdcircumferential distance and the fourth circumferential distance.
 7. Theframe of claim 1, further comprising a valve member attached to thesupport frame and moveable within the lumen to regulate fluid flowtherein, where the valve member is attached to the first member and ismoveable across the lumen between an open position permitting fluid flowthrough the lumen from the proximal end to the distal end, and a closedposition substantially preventing fluid flow through the lumen, thevalve member contacting the circumferential plane between the firstmember and the second member in the closed position.
 8. A support framesuitable for prosthetic implantable valves comprising: a proximalannular member longitudinally spaced from a distal annular memberaxially aligned with the proximal annular member around a longitudinalaxis; a plurality of longitudinal connecting members extendingsubstantially parallel to the longitudinal axis from the proximalannular member to the distal annular member and defining a hypotheticalcircumferential plane around an outer surface of the support frame anddefining a lumen extending from a proximal end to a distal end of thesupport frame around the longitudinal axis; the plurality oflongitudinal connecting members including a first member opposablypositioned across the lumen from a directly circumferentially adjacentsecond member without an intervening member disposed therebetween, athird member circumferentially adjacent to the first member, a fourthmember circumferentially adjacent to the third member, and a fifthmember circumferentially adjacent to the fourth member and the secondmember; wherein a first circumferential distance is disposed between thefirst member and the second member, a second circumferential distance isdisposed between the third member and the first member, a thirdcircumferential distance is disposed between the third member and thefourth member, a fourth circumferential distance is disposed between thefourth member and the fifth member, and a fifth circumferential distanceis disposed between the fifth member and the second member; wherein thefirst circumferential distance is greater than each of the secondcircumferential distance, the third circumferential distance, the fourthcircumferential distance, and the fifth circumferential distance; andwherein the circumferential distances are measured along thecircumferential plane perpendicular to the longitudinal axis at aposition between the proximal end and the distal end.
 9. The frame ofclaim 8, wherein the second circumferential distance is substantiallyequal to the fifth circumferential distance; and wherein the thirdcircumferential distance is substantially equal to the fourthcircumferential distance.
 10. The frame of claim 9, wherein the firstcircumferential distance between the first member and the second memberis substantially equal to the sum of the third circumferential distanceand the fourth circumferential distance.
 11. The frame of claim 8,wherein the second circumferential distance between the first member andthe third member is less than about 10% of the longitudinal length ofthe members; and wherein the fifth circumferential distance between thefifth member and the second member is less than about 10% of thelongitudinal length of the members.
 12. The frame of claim 8, wherein aradial angle of about (2π/4) radians is subtended by the sum of thethird circumferential distance and one half of the secondcircumferential distance.
 13. The frame of claim 8, wherein a radialangle of about (2π/2) radians is subtended by the sum of the firstcircumferential distance, one half of the second circumferentialdistance, and one half of the fifth circumferential distance.
 14. Theframe of claim 8, further comprising a valve member attached to thesupport frame and moveable within the lumen to regulate fluid flowtherein, where the valve member is attached to the first member and ismoveable across the lumen between an open position permitting fluid flowthrough the lumen from the proximal end to the distal end, and a closedposition substantially preventing fluid flow through the lumen, thevalve member contacting the circumferential plane between the firstmember and the second member in the closed position.
 15. A support framesuitable for prosthetic implantable valves comprising: a proximalannular member longitudinally spaced from a distal annular memberaxially aligned with the proximal annular member around a longitudinalaxis; a plurality of longitudinal connecting members extendingsubstantially parallel to the longitudinal axis from the proximalannular member to the distal annular member and defining a hypotheticalcircumferential plane around an outer surface of the support frame anddefining a lumen extending from a proximal end to a distal end of thesupport frame around the longitudinal axis; the plurality oflongitudinal connecting members including a first member opposablypositioned across the lumen from a directly circumferentially adjacentsecond member without an intervening member disposed therebetween, athird member circumferentially adjacent to the first member, a fourthmember circumferentially adjacent to the third member, and a fifthmember circumferentially adjacent to the fourth member and the secondmember; wherein a first circumferential distance is disposed between thefirst member and the second member, a second circumferential distance isdisposed between the third member and the first member, a thirdcircumferential distance is disposed between the third member and thefourth member, a fourth circumferential distance is disposed between thefourth member and the fifth member, and a fifth circumferential distanceis disposed between the fifth member and the second member; wherein thefirst circumferential distance is greater than each of the secondcircumferential distance, the third circumferential distance, the fourthcircumferential distance, and the fifth circumferential distance;wherein the second circumferential distance is substantially equal tothe fifth circumferential distance; wherein the third circumferentialdistance is substantially equal to the fourth circumferential distance;and wherein the circumferential distances are measured along thecircumferential plane perpendicular to the longitudinal axis at aposition between the proximal end and the distal end.
 16. The frame ofclaim 15, wherein the first circumferential distance between the firstmember and the second member is substantially equal to the sum of thethird circumferential distance and the fourth circumferential distance.17. The frame of claim 15, wherein the second circumferential distancebetween the first member and the third member is less than about 10% ofthe longitudinal length of the members; and wherein the fifthcircumferential distance between the fifth member and the second memberis less than about 10% of the longitudinal length of the members. 18.The frame of claim 15, wherein a radial angle of about (2π/4) radians issubtended by the sum of the third circumferential distance and one halfof the second circumferential distance.
 19. The frame of claim 15,wherein a radial angle of about (2π/2) radians is subtended by the sumof the first circumferential distance, one half of the secondcircumferential distance, and one half of the fifth circumferentialdistance.
 20. The frame of claim 15, further comprising a valve memberattached to the support frame and moveable within the lumen to regulatefluid flow therein, where the valve member is attached to the firstmember and is moveable across the lumen between an open positionpermitting fluid flow through the lumen from the proximal end to thedistal end, and a closed position substantially preventing fluid flowthrough the lumen, the valve member contacting the circumferential planebetween the first member and the second member in the closed position.